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P80075 (CCL8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-C motif chemokine 8
Alternative name(s):
HC14
Monocyte chemoattractant protein 2
Monocyte chemotactic protein 2
Short name=MCP-2
Small-inducible cytokine A8

Cleaved into the following chain:

  1. MCP-2(6-76)
Gene names
Name:CCL8
Synonyms:MCP2, SCYA10, SCYA8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length99 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils. May play a role in neoplasia and inflammatory host responses. This protein can bind heparin. The processed form MCP-2(6-76) does not show monocyte chemotactic activity, but inhibits the chemotactic effect most predominantly of CCL7, and also of CCL2 and CCL5 and CCL8. Ref.7

Subunit structure

Monomer or homodimer; in equilibrium. Ref.6

Subcellular location

Secreted.

Tissue specificity

Highest expression found in the small intestine and peripheral blood cells. Intermediate levels seen in the heart, placenta, lung, skeletal muscle, thymus, colon, ovary, spinal cord and pancreas. Low levels seen in the brain, liver, spleen and prostate.

Induction

By IFNG/IFN-gamma, mitogens and IL1/interleukin-1.

Post-translational modification

N-terminal processed form MCP-2(6-76) is produced by proteolytic cleavage after secretion from peripheral blood monocytes.

Sequence similarities

Belongs to the intercrine beta (chemokine CC) family.

Sequence caution

The sequence CAA68168.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processChemotaxis
Inflammatory response
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandHeparin-binding
   Molecular functionCytokine
   PTMDisulfide bond
Pyrrolidone carboxylic acid
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion transport

Inferred from direct assay PubMed 10734056. Source: UniProtKB

cell chemotaxis

Traceable author statement PubMed 9468473. Source: GOC

cell-cell signaling

Inferred from direct assay PubMed 10734056. Source: UniProtKB

cellular calcium ion homeostasis

Inferred from direct assay PubMed 10734056. Source: UniProtKB

chemotaxis

Traceable author statement PubMed 9468473. Source: ProtInc

exocytosis

Inferred from direct assay PubMed 10734056. Source: UniProtKB

immune response

Inferred from electronic annotation. Source: InterPro

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of catalytic activity

Inferred from direct assay PubMed 10734056. Source: GOC

protein phosphorylation

Inferred from direct assay PubMed 10734056. Source: GOC

response to virus

Traceable author statement PubMed 9468473. Source: ProtInc

signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionchemokine activity

Traceable author statement PubMed 9468473. Source: ProtInc

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

phospholipase activator activity

Inferred from direct assay PubMed 10734056. Source: UniProtKB

protein kinase activity

Inferred from direct assay PubMed 10734056. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Probable
Chain24 – 9976C-C motif chemokine 8
PRO_0000005188
Chain29 – 9971MCP-2(6-76)
PRO_0000005189

Amino acid modifications

Modified residue241Pyrrolidone carboxylic acid
Disulfide bond34 ↔ 59 Ref.8
Disulfide bond35 ↔ 75 Ref.8

Natural variations

Natural variant141A → V.
Corresponds to variant rs35401229 [ dbSNP | Ensembl ].
VAR_048704
Natural variant691K → Q. Ref.1 Ref.2 Ref.3
Corresponds to variant rs1133763 [ dbSNP | Ensembl ].
VAR_001633

Secondary structure

.............. 99
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P80075 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 9D67976BB9422F2A

FASTA9911,246
        10         20         30         40         50         60 
MKVSAALLCL LLMAATFSPQ GLAQPDSVSI PITCCFNVIN RKIPIQRLES YTRITNIQCP 

        70         80         90 
KEAVIFKTKR GKEVCADPKE RWVRDSMKHL DQIFQNLKP 

« Hide

References

« Hide 'large scale' references
[1]"The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2."
van Coillie E., Fiten P., Nomiyama H., Sakaki Y., Miura R., Yoshie O., van Damme J., Opdenakker G.
Genomics 40:323-331(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-69.
[2]"Human monocyte chemotactic protein-2: cDNA cloning and regulated expression of mRNA in mesenchymal cells."
van Coillie E., Froyen F., Nomiyama H., Miura R., Fiten P., van Aelst I., van Damme J., Opdenakker G.
Biochem. Biophys. Res. Commun. 231:726-730(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-69.
Tissue: Bone marrow.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-69.
[4]"Cloning and expression of a gamma-interferon-inducible gene in monocytes: a new member of a cytokine gene family."
Chang H.C., Hsu F., Freeman G.J., Griffin J.D., Reinherz E.L.
Int. Immunol. 1:388-397(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-99.
[5]"Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family."
van Damme J., Proost P., Lenaerts J.-P., Opdenakker G.
J. Exp. Med. 176:59-65(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-99.
Tissue: Osteosarcoma.
[6]"Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3."
Kim K.-S., Rajarathnam K., Clark-Lewis I., Sykes B.D.
FEBS Lett. 395:277-282(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[7]"Posttranslational modifications affect the activity of the human monocyte chemotactic proteins MCP-1 and MCP-2: identification of MCP-2(6-76) as a natural chemokine inhibitor."
Proost P., Struyf S., Couvreur M., Lenaerts J.-P., Conings R., Menten P., Verhaert P., Wuyts A., Van Damme J.
J. Immunol. 160:4034-4041(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF MCP-2(6-76), IDENTIFICATION BY MASS SPECTROMETRY, PROTEOLYTIC PROCESSING OF N-TERMINAL, FUNCTION.
[8]"Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors."
Blaszczyk J., Coillie E.V., Proost P., Damme J.V., Opdenakker G., Bujacz G.D., Wang J.M., Ji X.
Biochemistry 39:14075-14081(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-99, PYROGLUTAMATE FORMATION AT GLN-24, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Wikipedia

CCL8 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X99886 Genomic DNA. Translation: CAA68168.1. Different initiation.
Y10802 mRNA. Translation: CAA71760.1.
Y16645 mRNA. Translation: CAA76341.1.
BC126242 mRNA. Translation: AAI26243.1.
CCDSCCDS11280.1.
PIRJC5295.
RefSeqNP_005614.2. NM_005623.2.
UniGeneHs.271387.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ESRX-ray2.00A24-99[»]
ProteinModelPortalP80075.
SMRP80075. Positions 24-99.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112258. 2 interactions.
DIPDIP-5871N.
MINTMINT-103111.
STRING9606.ENSP00000225840.

Polymorphism databases

DMDM2506280.

Proteomic databases

PaxDbP80075.
PRIDEP80075.

Protocols and materials databases

DNASU6355.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000394620; ENSP00000378118; ENSG00000108700.
GeneID6355.
KEGGhsa:6355.
UCSCuc002hib.3. human.

Organism-specific databases

CTD6355.
GeneCardsGC17P032646.
HGNCHGNC:10635. CCL8.
MIM602283. gene.
neXtProtNX_P80075.
PharmGKBPA35567.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG75507.
HOGENOMHOG000036686.
HOVERGENHBG017871.
InParanoidP80075.
KOK16596.
OMAQKLESYT.
OrthoDBEOG7C5MC2.
PhylomeDBP80075.
TreeFamTF334888.

Gene expression databases

ArrayExpressP80075.
BgeeP80075.
CleanExHS_CCL8.
GenevestigatorP80075.

Family and domain databases

InterProIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamPF00048. IL8. 1 hit.
[Graphical view]
SMARTSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMSSF54117. SSF54117. 1 hit.
PROSITEPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCCL8. human.
EvolutionaryTraceP80075.
GeneWikiCCL8.
GenomeRNAi6355.
NextBio24684.
PMAP-CutDBP80075.
PROP80075.
SOURCESearch...

Entry information

Entry nameCCL8_HUMAN
AccessionPrimary (citable) accession number: P80075
Secondary accession number(s): A0AV77, P78388
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM